Cysteine is an important amino acid in sulfur metabolism of all living organisms. It is used in the biosynthesis of proteins, such as hair keratin, glutathione, biotin, methionine and other sulfur-containing metabolites, or used as a precursor of coenzyme A. In addition, the biosynthesis of cysteine is known to be closely associated with the biosynthesis of other amino acids like serine, glycine, and methionine. Industrially, cysteine and its derivatives are used in a various fields including the pharmaceutical industry (for treatment of bronchial diseases), the cosmetics industry (in hair shampoo, compositions for permanent waves), and the food industry (antioxidants, flavor enhancers, dough softeners).
Until now, cysteine has been produced chemically by acid hydrolysis of raw materials such as human hairs or animal feathers. However, not only a yield of the production of cysteine from hairs is as low as 7˜8%, but also the use of hydrochloric acid or sulfuric acid cause a lot of waste resulting in environmental pollution. Further, the use of hairs as a raw material may induce the user to have a strong aversion thereto. These problems have caused a push for the development of environment-friendly production processes of cysteine. Therefore, a method of producing cysteine using microorganisms has been developed.
Representative microbial production of cysteine is 1) the biological conversion of D, L-ATC using a microorganism. This conversion process is, however, difficult to apply industrially due to the low solubility of the precursor D, L-ATC. 2) Another method of cysteine production is direct fermentation using E. coli. In this method, excessive accumulation of cysteine within microorganisms may incurs intracellular toxicity, and there's a limitation in the production of cysteine at a high concentration by using microorganism.
Referring to one of the biosynthesis pathways of cysteine in microorganisms and plants, O-acetyl-serine (OAS) acts as an intermediate precursor providing the carbon backbone of cysteine. O-acetylserine sulfhydrylase (OASS), using hydrogen sulfide as a sulfur donor, catalyses the conversion of OAS to cysteine. Therefore, cysteine can be produced from microorganisms accumulating OAS and various sulfur donors using OASS (U.S. Pat. No. 6,579,705).
The present inventors investigated a novel method for producing cysteine unlike the conventional method, and they discovered the existence of O-phosphoserine sulfhydrylase (OPSS) catalyzing synthesis of cysteine from O-phosphoserine (OPS) in a particular microorganism. OPS is an intermediate precursor of L-serine and has a shorter metabolic pathway than OAS. Thus, use of OPS can be advantageous, compared to use of OAS. In particular, it was found that OPSS derived from Trichomonas vaginalis does not require sulfer transferring coenzymes such as mec+ and cys0, unlike OPSS derived from Mycobacterium tuberculosis, and also shows optimal activity at 37° C., unlike OPSS derived from Aeropyrum pernix. 